Dr. Syed Badshah
Crude drug Structure Ligand bindingReceptor
A chemical structure includes molecular geometry,
electronic structure, and crystal structure of a molecule.
Biological activity is an expression describing the beneficial
or adverse effects of a drug on living matter.
STRUCTURE ACTIVITY RELATIONSHIP
The relationship between the chemical or 3D
structure of a molecule and its biological activity.
Enables the determination of the chemical groups
responsible for evoking a target biological effect in
WHY SAR Exist?
• The interaction of the drug molecule with protein depends
on its chemical structure
NEED OF SAR STUDY
• A study of the structure–activity relationship is mainly
done by lead molecule.
• It is used to determine pharmacophore, unwanted side
• To develop a new drug that has increased activity.
• To determine some different activity from an
• To fewer unwanted side effects
• To know the changes in pharmacological properties
by performing minor changes in the drug molecule
A B C
Rings A–D are essential for activity. Saturation of ring B< activity
necessary for activity
essential for activity, S N
D-ring pyridone is required for anti
Modifications in rings A, B are well tolerated
The stereochemistry at C-20 is very crucial as
20(S) hydroxyl is active, 20(R) inactive
modifications at the C , D rings led
to complete loss of cytotoxicity.
Modification in rings A,B
Modification in rings C,D
In general, modifications at the C and D rings of
camptothecin led to complete loss of cytotoxicity.
If we see these rings, the only positions available
for modifications are C-5, C-14 and C-17. Several
derivatives have been reported either with less
activity or with loss of activity.
Modification in ring E
The α- hydroxyl lactone system of ring E has been
found to be important for the inhibition of the
topoisomerase enzyme as well as for in vivo
Derivatives having a lactam group instead of a
lactone, were devoid of topoisomerase inhibitor
Taxol, paclitaxel, trade name taxol,
by Dr. WALL and Dr. WANI
Pacific yew, Taxus
isoserine side chain, at
the C-13 hydroxyl as an
Oxitane ring essential
Reduction enhance activity
Removal of acetyl < activity
Phenyl isoserine chain essential for activity
N-acyl group, required
Aryl group, essential
Free OH active in both(in vivo, in vitro)
Ester only in vivo
The C-3’aryl group is required for better
activity, methyl group, activity is reduced19-
northern and southern hemispheres.
modifications in the southern hemisphere are strictly forbidden
while in the northern hemisphere are allowed
C-13 SIDE CHAIN
C-13 side chain is essentially required for anticancer
activity. The C-2’-hydroxyl is important for activity.
When this hydroxyl is protected, activity is reduced to a
great extent and if the protection is made with a labile
group it shows similar activity in vivo, while no activity is
shown in in vitro testing